Oligonucleotide manufacturing efficiency and sustainability: findings from a cross-sector expert meeting
Nucleic Acid Insights 2026; 3(8), 465–478
DOI: 10.18609/nai.2026.063
Expert consensus and recommendations from the inaugural Nucleic Acid Insights Special Interest Group on Oligonucleotide Manufacturing Efficiency and Sustainability, April 28–29, 2026.
The oligonucleotide therapeutics sector is currently in the midst of a transition from rare-disease to large-indication manufacturing, and the infrastructure, methods, and commercial frameworks built for low-volume programs are struggling to keep up. This article presents expert consensus and recommendations from the inaugural Nucleic Acid Insights Special Interest Group on Oligonucleotide Manufacturing Efficiency and Sustainability (April 2026). Over the course of 2 days, cross-sector working groups covered established and emerging synthesis platforms, solvent strategy, downstream processing, analytical tools, conjugate modalities, and commercial manufacturing strategy. Expert consensus identified six priority areas: earlier platform commitment at pre-IND stage; pre-competitive collaboration on solvent recycling; empirical limit-setting for residual synthesis enzymes; integrated upstream – downstream process development; coordinated generation of the data regulators will need to guide novel impurity class assessment; and early qualification of supply chains for critical starting materials. The result is a practical set of priorities for organizations navigating this transition now.